Inhibition of CHI3L1 attenuates excessive autophagy in intestinal epithelial cells to reduce the severity of necrotizing enterocolitis DOI Creative Commons

Y Li,

Wenqiang Sun,

Xinyun Jin

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 5, 2025

Abstract Neonatal necrotizing enterocolitis (NEC) is a devastating intestinal disease that primarily affects preterm infants. Unfortunately, no specific treatment for NEC currently available, making it crucial to further investigate its underlying mechanisms. In this study, we aimed identify the key target gene, CHI3L1, which was significantly upregulated in tissues of both affected children and model mice from GEO database. CHI3L1 known play important roles inflammatory immune responses, as well tissue damage repair, all are closely associated with development NEC. We conducted validations at cellular animal levels, demonstrating inhibition or knockdown reduced severity Mechanistic investigations revealed inhibited PI3K-Akt-FoxO1 signalling pathway, alleviating excessive autophagy epithelial cells subsequently reducing injury responses. Clinical studies have elevated serum expression paediatric patients occurrence necrotising NEC, positive correlations Duke Abdominal Assessment Scale (DAAS), C-reactive protein (CRP), procalcitonin (PCT), red cell distribution width (RDW), lactate dehydrogenase (LDH) levels. conclusion, our findings confirmed close relationship between suggesting may mitigate responses by cells. Therefore, targeting be an effective strategy combat

Language: Английский

Inhibition of CHI3L1 attenuates excessive autophagy in intestinal epithelial cells to reduce the severity of necrotizing enterocolitis DOI Creative Commons

Y Li,

Wenqiang Sun,

Xinyun Jin

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 5, 2025

Abstract Neonatal necrotizing enterocolitis (NEC) is a devastating intestinal disease that primarily affects preterm infants. Unfortunately, no specific treatment for NEC currently available, making it crucial to further investigate its underlying mechanisms. In this study, we aimed identify the key target gene, CHI3L1, which was significantly upregulated in tissues of both affected children and model mice from GEO database. CHI3L1 known play important roles inflammatory immune responses, as well tissue damage repair, all are closely associated with development NEC. We conducted validations at cellular animal levels, demonstrating inhibition or knockdown reduced severity Mechanistic investigations revealed inhibited PI3K-Akt-FoxO1 signalling pathway, alleviating excessive autophagy epithelial cells subsequently reducing injury responses. Clinical studies have elevated serum expression paediatric patients occurrence necrotising NEC, positive correlations Duke Abdominal Assessment Scale (DAAS), C-reactive protein (CRP), procalcitonin (PCT), red cell distribution width (RDW), lactate dehydrogenase (LDH) levels. conclusion, our findings confirmed close relationship between suggesting may mitigate responses by cells. Therefore, targeting be an effective strategy combat

Language: Английский

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